A Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine+Obinutuzumab (GA101) in Participants With Rituximab-Refractory, Indolent Non-Hodgkin's Lymphoma (GADOLIN)
An Open-Label, Multicenter, Randomized, Phase III Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine+RO5072759 (GA101) in Patients With Rituximab-Refractory, Indolent Non-Hodgkin's Lymphoma
3 other identifiers
interventional
413
14 countries
121
Brief Summary
This open-label, multicenter, randomized Phase III study will investigate the efficacy, safety, pharmacokinetics and pharmacoeconomics of obinutuzumab (RO5072759, GA101) combined with bendamustine followed by continued obinutuzumab treatment (maintenance monotherapy) compared with bendamustine alone treatment in participants with rituximab-refractory indolent Non-Hodgkin's lymphoma (iNHL). The end of study was defined to when safety follow-up for all patients had been completed (2 years' safety follow-up from last dose).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Apr 2010
Longer than P75 for phase_3
121 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 28, 2010
CompletedFirst Posted
Study publicly available on registry
February 1, 2010
CompletedStudy Start
First participant enrolled
April 30, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2014
CompletedResults Posted
Study results publicly available
November 17, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 30, 2018
CompletedJanuary 13, 2020
December 1, 2019
4.4 years
January 28, 2010
September 27, 2016
December 20, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants With Progressive Disease (PD) as Assessed by Independent Review Committee (IRC) or Death
PD was assessed by an IRC according to the modified response criteria for indolent Non-Hodgkin's Lymphoma (iNHL) (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion more than 1.5 centimeters (cm) in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50 percent (%) increase from nadir in the sum of product diameter (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions (example: splenic or hepatic nodules). To be considered PD, a lymph node with a diameter of the short axis of less than (\<) 1.0 cm must increase by greater than or equal to (≥) 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node greater than (\>) 1 cm in its short axis.
Baseline until PD or death, whichever occurred first (assessed at baseline, 14 days prior to Cycle [Cy] 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1, then every 3 months up to 2 years and every 6 months for next 2 years [up to 4.5 years overall])
Progression-Free Survival (PFS) as Assessed by IRC
PFS was defined as the time from randomization to the first occurrence of PD or death as assessed by an IRC according to the modified response criteria for iNHL (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). To be PD, a lymph node with a diameter of the short axis of \<1.0 cm must increase by ≥ 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node \>1 cm in its short axis. PFS was estimated using Kaplan-Meier method and 95% confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.
Baseline until PD or death, whichever occurred first (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28-42 days after Cy 6 Day 1, then every 3 months up to 2 years and every 6 months for next 2 years [up to 4.5 years overall])
Secondary Outcomes (31)
Number of Participants With PD or Death as Assessed by Investigator
Baseline until PD or death, whichever occurred first (up to 8.5 years overall))
PFS as Assessed by Investigator
Baseline until PD or death, whichever occurred first (up to 8.5 years overall)
Percentage of Participants With Objective Response as Assessed by IRC
Baseline until PD or death, whichever occurred first (up to approximately 5 years)
Percentage of Participants With Objective Response as Assessed by Investigator
Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)
Percentage of Participants With Best Overall Response (BOR) as Assessed by IRC
Baseline until PD or death, whichever occurred first (up to approximately 5 years)
- +26 more secondary outcomes
Study Arms (2)
Bendamustine Alone
ACTIVE COMPARATORParticipants will receive bendamustine 120 milligrams per meter square (mg/m\^2) Intravenous (IV) infusion on Days 1 and 2 of each 28-day cycle for up to six cycles.
Obinutuzumab + Bendamustine
EXPERIMENTALInduction phase: Participants will receive bendamustine 90 mg/m\^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants will also receive obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with complete response (CR), partial response (PR) or stable response (SD) then will receive obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurs first).
Interventions
Eligibility Criteria
You may qualify if:
- History of histologically documented, B-lymphocyte antigen cluster of differentiation 20 plus (CD20+), iNHL
- Refractory to any previous regimen containing rituximab (defined by participants who did not respond or who progressed during or up to 6 months after treatment with rituximab or a rituximab-containing regimen)
- Previously treated with a maximum of four unique chemotherapy containing treatment regimens
- All participants must have at least one bi-dimensionally measurable lesion (greater than \[\>\]1.5 centimeters (cm) in its largest dimension by computed tomography \[CT\] scan)
You may not qualify if:
- Prior use of any monoclonal antibody (other than anti-CD20) within 3 months prior to the start of Cycle 1, prior treatment with obinutuzumab was not allowed
- Chemotherapy or other investigational therapy within 28 days prior to the start of Cycle 1
- Prior treatment with bendamustine (within 2 years of the start of Cycle 1)
- Prior allogeneic stem cell transplant
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- History of sensitivity to mannitol
- Central nervous system lymphoma or prior diffuse large B-cell lymphoma (DLBCL), histological evidence of transformation to high grade or diffuse large B-cell lymphoma
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 4 weeks
- Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
- Vaccination with a live vaccine a minimum of 28 days prior to randomization
- Recent major surgery (within 4 weeks), other than for diagnosis
- Presence of positive test results for Hepatitis B surface antigen (HBsAg); antibody to hepatitis B core antigen \[anti-HBc\]) with detectable viral load (positive hepatitis B virus \[HBV\] deoxyribo-nucleic acid \[DNA\]) or Hepatitis C
- Participants with chronic hepatitis B or seropositive occult (HBV) infection
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
- Roche Pharma AGcollaborator
Study Sites (121)
Southern Cancer Center, PC
Mobile, Alabama, 36608, United States
Dr. Donald W. Hill, MD, FACP
Casa Grande, Arizona, 85122, United States
Highlands Oncology Group
Rogers, Arkansas, 72758, United States
Kaiser Permanente - Bellflower
Bellflower, California, 90706, United States
Bay Area Cancer Research Group, LLC
Pleasant Hill, California, 94523, United States
Sharp Memorial Hospital
San Diego, California, 92123, United States
Georgetown University Medical Center Lombardi Cancer Center
Washington D.C., District of Columbia, 20007, United States
Washington DC VA Med Center; Hematology
Washington D.C., District of Columbia, 20422, United States
University of Florida
Gainesville, Florida, 32607, United States
University of Florida; Division of Hematology/Oncology
Gainesville, Florida, 33610-0277, United States
Md Anderson Cancer Center Orlando
Orlando, Florida, 32806, United States
Rush Cancer Institute
Chicago, Illinois, 60612, United States
Quincy Medical Group
Quincy, Illinois, 62301, United States
Simmons Cancer Institute
Springfield, Illinois, 62794-9677, United States
University of Iowa
Iowa City, Iowa, 52242, United States
Univ Louisville School of Med
Louisville, Kentucky, 40202, United States
New England Cancer Specialists
Scarborough, Maine, 04074, United States
Meritus Center for Clinical Research
Hagerstown, Maryland, 21740, United States
Capitol Comprehensive CA Care
Jefferson City, Missouri, 65101, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Hematology Oncology Assoc SJ
Mount Holly, New Jersey, 08060, United States
San Juan Oncology
Farmington, New Mexico, 87401, United States
The Mark H. Zangmeister Ctr; Mid Ohio Onc/Hem Inc.
Columbus, Ohio, 43219, United States
OHSU Knight Cancer Institute
Portland, Oregon, 97210, United States
Pacific Oncology, PC
Portland, Oregon, 97210, United States
OHSU Ctr for Health & Healing
Portland, Oregon, 97239, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224, United States
Sanford Health System
Sioux Falls, South Dakota, 57105, United States
South Texas Inst of Cancer
Corpus Christi, Texas, 78405, United States
University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Univ of Wisconsin Hosp & Clin
Madison, Wisconsin, 53792, United States
Lkh-Univ. Klinikum Graz
Graz, 8036, Austria
Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.
Salzburg, 5020, Austria
Medizinische Universität Wien
Vienna, 1090, Austria
ZNA Stuivenberg
Antwerp, 2060, Belgium
AZ Groeninge
Kortrijk, 8500, Belgium
CHU Ambroise Paré
Mons, 7000, Belgium
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
British Columbia Cancer Agency
Kelowna, British Columbia, V1Y 5L3, Canada
British Columbia Cancer Agency
Vancouver, British Columbia, V5Z 1H6, Canada
Manitoba Cancer Care
Winnipeg, Manitoba, R3E 0V9, Canada
Moncton Hospital
Moncton, New Brunswick, E1C 6Z8, Canada
Toronto East General Hospital; Main Pharmacy G Wing Basement
East York, Ontario, M4C 3E7, Canada
Princess Margaret Hospital
Toronto, Ontario, M4X 1K9, Canada
CHUM-Hosp Notre Dame
Montreal, Quebec, H2X 3E4, Canada
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
Montreal, Quebec, H3T 1E2, Canada
CHA Hopital de I enfant-Jesus
Québec, Quebec, G1J 1Z4, Canada
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1, Canada
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
Brno, 625 00, Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05, Czechia
I Interni klinika; Vseobecna fakultni nemocnice
Prague, 128 08, Czechia
Institut Bergonie; Hematologie Oncologie
Bordeaux, 33076, France
Polyclinique Bordeaux Nord
Bordeaux, 33300, France
Hopital Henri Mondor
Créteil, 94010, France
CH Dijon
Dijon, 21079, France
Centre d'oncologie-radiotherap
LeMans, 72015, France
Hopital Claude Huriez
Lille, 59037, France
Centre Leon Berard
Lyon, 69008, France
Hopital Bon Secour
Metz, 57038, France
CHU Hopital Saint Eloi
Montpellier, 34295, France
Hopital Hotel Dieu Et Hme; Clinique Dermatologique
Nantes, 44093, France
Hopital Necker
Paris, 75015, France
Hopital Saint Louis; Dermatologie 1
Paris, 75475, France
CHU Bordeaux
Pessac, 33604, France
Centre Hospitalier Lyon Sud; Hematolgie
Pierre-Bénite, 69495, France
Chu De Poitiers; Chu La Miletrie
Poitiers, 86021, France
CHU de Reims
Reims, 51100, France
Hopital Pontchaillou
Rennes, 35033, France
Centre Henri Becquerel
Rouen, 76038, France
Clinique Ste Anne
Strasbourg, 67000, France
CHRU de; Maladies, Vasculaires
Vandœuvre-lès-Nancy, 54511, France
St. Johannes Hospital Duisburg
Duisburg, 47166, Germany
Klinikum Frankfurt Höchst
Frankfurt am Main, 65929, Germany
Asklepios Klinik St. Georg
Hamburg, 20099, Germany
Universitaetsklinikum Leipzig
Leipzig, 04103, Germany
Klinikum der Universitat Munchen, Campus Grobhadern;; Medizinische Klinik und Poliklinik III
München, 81377, Germany
Schwarzwald-Baar Klinikum GmbH
Villingen-Schwenningen, 78052, Germany
Ospedale Vito Fazzi
Lecce, Apulia, 73100, Italy
Azienda Ospedaliera Universitaria di Modena
Modena, Emilia-Romagna, 41100, Italy
Azienda Ospedaliera Univ, Ematologica
Udine, Friuli Venezia Giulia, 33100, Italy
Azienda Ospedaliera Univ
Rome, Lazio, 00133, Italy
Universita La Sapienza
Rome, Lazio, 00161, Italy
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
Milan, Lombardy, 20133, Italy
Irccs Policlinico San Matteo; Divisione Di Ematologia
Pavia, Lombardy, 27100, Italy
Azienda Ospedale San Giovanni
Turin, Piedmont, 10126, Italy
Ospedale Mauriziano Umberto I
Turin, Piedmont, 10128, Italy
Azienda Ospedaliero Univ
Catania, Sicily, 95124, Italy
Azienda Ospedaliera Univ
Florence, Tuscany, 50141, Italy
VU MEDISCH CENTRUM; Dept. of Medical Oncology
Amsterdam, 1081 HV, Netherlands
Albert Schweitzer Ziekenhuis
Dordrecht, 3371 NM, Netherlands
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ, Netherlands
Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology
Rotterdam, 3015 CE, Netherlands
Erasmus MC
Rotterdam, 3015 GD, Netherlands
Haga Ziekenhuis
The Hague, 2504 LN, Netherlands
Regional Oncology Hospital
Irkutsk, 664035, Russia
Blokhin Cancer Research Center; Combined Treatment
Moscow, 115478, Russia
City Clin Hosp n.a. S.P.Botkin
Moscow, 125101, Russia
Russian Hema Res Ctr of RAMS
Moscow, 125167, Russia
Republican Clinical Hospital n.a. Baranov; Haematology
Petrozavodsk, 185019, Russia
Ryazan Regional Clinical Hosp
Ryazan, 390039, Russia
SRI of Hematology and Transfusiology
Saint Petersburg, 191024, Russia
St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta
Saint Petersburg, 197022, Russia
Clinica Universitaria de Navarra
Pamplona, Navarre, 31008, Spain
Hospital Univ. Nuestra Señora de Valme;
Sevillac, Sevilla, 41014, Spain
Hospital Universitario Basurto
Bilbao, Vizcaya, 48013, Spain
Hospital Universitario de la Princesa; Servicio de Hematologia
Madrid, 28006, Spain
Hospital Universitario La Paz
Madrid, 28034, Spain
Skånes University Hospital, Skånes Department of Onclology
Lund, 22185, Sweden
Hematology Center; Karolinska Univ Hosp
Stockholm, 14186, Sweden
Norrlands Uni Hospital; Onkologi Avd.
Umeå, 901 85, Sweden
Onc Clin, Akademiska Sjukhuset
Uppsala, 751 85, Sweden
Universitaetsspital Basel; Onkologie
Basel, 4031, Switzerland
Inselspital Bern; Universitätsklinik für medizinische Onkologie
Bern, 3010, Switzerland
Kantonsspital Graubünden;Onkologie und Hämatologie
Chur, 7000, Switzerland
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
Leicester Royal Infirmary
Leicester, LE1 5WW, United Kingdom
Barts & London School of Med; Medical Oncology
London, EC1A 7BE, United Kingdom
Freeman Hospital
Newcastle upon Tyne, NE7 7DN, United Kingdom
Singleton Hospital; Pharmacy Department
Swansea, SA2 8QA, United Kingdom
Related Publications (4)
Pott C, Sehn LH, Belada D, Gribben J, Hoster E, Kahl B, Kehden B, Nicolas-Virelizier E, Spielewoy N, Fingerle-Rowson G, Harbron C, Mundt K, Wassner-Fritsch E, Cheson BD. MRD response in relapsed/refractory FL after obinutuzumab plus bendamustine or bendamustine alone in the GADOLIN trial. Leukemia. 2020 Feb;34(2):522-532. doi: 10.1038/s41375-019-0559-9. Epub 2019 Aug 28.
PMID: 31462735DERIVEDGibiansky E, Gibiansky L, Buchheit V, Frey N, Brewster M, Fingerle-Rowson G, Jamois C. Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Br J Clin Pharmacol. 2019 Sep;85(9):1935-1945. doi: 10.1111/bcp.13974. Epub 2019 Jul 12.
PMID: 31050355DERIVEDCheson BD, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall Survival Benefit in Patients With Rituximab-Refractory Indolent Non-Hodgkin Lymphoma Who Received Obinutuzumab Plus Bendamustine Induction and Obinutuzumab Maintenance in the GADOLIN Study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. doi: 10.1200/JCO.2017.76.3656. Epub 2018 Mar 27.
PMID: 29584548DERIVEDSehn LH, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-1093. doi: 10.1016/S1470-2045(16)30097-3. Epub 2016 Jun 23.
PMID: 27345636DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Genentech
Study Officials
- STUDY DIRECTOR
Clinical Trials
Genentech, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 28, 2010
First Posted
February 1, 2010
Study Start
April 30, 2010
Primary Completion
September 30, 2014
Study Completion
November 30, 2018
Last Updated
January 13, 2020
Results First Posted
November 17, 2016
Record last verified: 2019-12